This is a proposal for continuation of an ongoing program-project grant (MH 23861) in which the central theme is the relationship between neuroregulators compounds which may function as neurotransmitters or neuromodulators--and behavior. The compounds which we are investigating are the catecholamines (epinephrine, norepinephrine, and dopamine); the idoleamines (serotonin and melatonin); acetylcholine; and certain peptides found in brain, particularly enkephalin. We are investigating the mechanisms which control the formation of these compoundss, the ways in which their analysis can be improved, and their relations to behavior both in animals and humans. We propose to continue a five-pronged research plan including studies centered about: I. Biochemical Regulation, II. Analytical Procedures, III. Endocrine Processes, IV. Behavioral Neurochemistry and Pharmacology and V. Clinical Processes. An ongoing interdisciplinary group has been brought together for these studies, which have a strong basic science component that interacts with and is essential for the clinical studies. The focus for the clinical studies consists of biochemical and endocrinological investigations of defined populations testing specific hypotheses. The methods which will be used are primarily those of biochemical pharmacology, but those methods are related to a variety of behavioral and clinical areas. We are interested in improving analytical procedures, and for many of our studies we would use mass fragmentographic, radioenzymatic, and radioimmunologic techniques.